This was a Phase II, randomized, partially double-blinded trial to determine virologic responses to new nucleoside regimens after prolonged ZDV or ddI monotherapy. Subjects were randomized to one of two treatment arms in a double-blinded fashion and followed for 48 weeks. All subjects were stratified at entry according to whether they were ZDV experienced or naive when they enrolled in ACTG 175. Group 1: (Prior ZDV) d4T 40 mg b.i.d. plus ZDV placebo tid plus 3TC placebo b.i.d. or d4T placebo b.i.d. plus ZDV 200mg tid plus 3TC 150mg b.i.d. Group 2: (Prior ddI) ZDV 200 mg t.i.d. plus ddI 200 mg b.i.d. plus 3TC placebo or ZDV 200 mg t.i.d. plus ddI placebo plus 3TC 150 mg b.i.d. The primary goals outlined in this trial were to determine the influence of viral load and CD4+ T-cell counts, biologic phenotype and the presence of symptoms of HIV disease, on responses to new therapeutic regimens in HIV-infected individuals; to determine the relationship between viral load and CD4+ T-cells, biologic phenotype and the presence of symptoms of HIV disease on the development of polymerase gene mutations; and to determine the antiviral effects within the defined treatment groups, who had been treated with either ZDV or ddI monotherapy while participating in ACTG 175. There were 229 patients enrolled nationwide following closure to enrollment on January 12, 1996. Subjects were unblinded to their assigned treatment regimen beginning 21 February 1997. Those subjects who were on treatment/on study at the time of unblinding were allowed to continue on the open-label extension until July 14, 1997 when ACTG 364 (a rollover protocol for ACTG 302) was approved for implementation. ACTG 364 is designed to compare the virologic efficacy of Nelfinavir and/or DMP-266 in combination with one or two new nucleoside analogs in nucleoside experienced subjects.